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PURPOSE: Canonical bone morphogenetic protein signaling plays a central role in endochondral bone development and trauma-induced heterotopic ossification (HO). However, the role of noncanonical bone morphogenetic protein signaling through the transforming growth factor-activated kinase (TAK1) pathway has not been evaluated in HO. We hypothesize that the TAK1 pathway is crucial for endochondral bone development and HO.

CONCLUSIONS: TAK1 plays a prominent role in chondrogenesis during limb development and ectopic bone formation, confirmed by abnormal bone growth and diminished HO in knockout mice. NG-25 appears to be a candidate drug for TAK1 inhibition, which we will evaluate for the treatment of HO using our burn/tenotomy model.